Hot off the presses! Nov 01 Nat Rev Immunol

The Nov 01 issue of the Nat Rev Immunol is now up on Pubget (About Nat Rev Immunol): if you're at a subscribing institution, just click the link in the latest link at the home page. (Note you'll only be able to get all the PDFs in the issue if your institution subscribes to Pubget.)

Latest Articles Include:

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  - Nat Rev Immunol 10(11):745 (2010)
  
• Toll-like receptors: Two for the price of one | PDF (158 KB)
  - Nat Rev Immunol 10(11):746 (2010)
  The enormous complexity of the mammalian immune system in terms of the variety of responses to different triggers belies the smaller number of receptors and signalling pathways that are used. This study explains one example of such economy by showing how one receptor can activate two signalling pathways, and it identifies receptor location as the determining factor.
• B cells: Survival centre | PDF (228 KB)
  - Nat Rev Immunol 10(11):747 (2010)
  During an adaptive immune response, pro- and anti-apoptotic molecules control lymphocyte survival and are crucial for shaping the magnitude and duration of the response. Now, reporting in Science, David Tarlinton and co-workers show that the anti-apoptotic molecule myeloid cell leukaemia sequence 1 (MCL1) is crucial for germinal centre B cell responses and suggest that distinct mechanisms control the survival of germinal centre and memory B cells.
• T cell responses: Exhaustion through BATF | PDF (215 KB)
  - Nat Rev Immunol 10(11):747 (2010)
  T cell exhaustion is a feature of chronic viral infections, such as HIV, and is associated with the increased expression of inhibitory receptors, such as programmed cell death 1 (PD1), by T cells. New research published in Nature Medicine shows that the activation of basic leucine zipper transcription factor ATF-like (BATF) is one of the pathways by which PD1 ligation impairs the function of HIV-specific CD8+ T cells.
• Inflammation: IAPP stokes the pancreatic fire | PDF (234 KB)
  - Nat Rev Immunol 10(11):748 (2010)
  Insulin resistance, dysfunction of islet β-cells and amyloid deposits in the pancreas are characteristics of type 2 diabetes. Recent evidence has suggested that inflammation may also have a pathogenic role in this disease and that interleukin-1β (IL-1β) is the main cytokine involved.
• Innate immunity: A new vein of TLR biology | PDF (332 KB)
  - Nat Rev Immunol 10(11):748 (2010)
  Inflammation and angiogenesis are intimately related processes and contribute to essential physiological responses, such as host defence and wound healing, but also promote tumour growth and metastasis. In a recent edition of Nature, West et al.
• How the pre-TCR self-associates | Immunoreceptor complex assembly | PDF (155 KB)
  - Nat Rev Immunol 10(11):749 (2010)
  Unlike the αβ-T cell receptor (αβTCR), the pre-TCR does not need to be ligated to induce dimerization and signalling. By analysing the structure of the pre-TCR, this study shows how ligand-independent dimerization occurs and how this allows the invariant pre-TCR α-chain (pre-Tα) to sense the correct folding of its various partner TCR β-chains.
• Neuroimmunology: The TH17 kiss of death for neurons | PDF (197 KB)
  - Nat Rev Immunol 10(11):750 (2010)
  T helper 17 (TH17) cells are known to have a central role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, but the full extent of their contribution has yet to be fully elucidated. Now, a study published in Immunity shows that TH17 cells directly interact with neurons during EAE, resulting in neuronal dysfunction and exacerbation of disease.
• Metabolism and immunology: Macrophages yo-yo during weight loss | PDF (229 KB)
  - Nat Rev Immunol 10(11):750 (2010)
  Obesity is associated with the accumulation of macrophages in adipose tissues (fat), where these cells contribute to local and systemic inflammation and the modulation of metabolic processes. But until now, no careful analysis of the macrophage response to weight loss had been carried out.
• T cell memory | Inflammation | Transplantation | PDF (141 KB)
  - Nat Rev Immunol 10(11):751 (2010)
  Memory T cells persisting within the brain after local infection show functional adaptations to their tissue of residence Wakim, L. M., Woodward-Davis, A. & Bevan, M. J.Proc. Natl Acad. Sci. USA5 Oct 2010 (doi: 10.1073/pnas.1010201107)
• Immune regulation: Controlling neutrophil plasticity | PDF (198 KB)
  - Nat Rev Immunol 10(11):752 (2010)
  Recently, neutrophils have been found to have previously unanticipated plasticity, being able to take on either a pro-inflammatory or an anti-inflammatory phenotype. Now, a study in Nature Immunology shows that this plasticity is regulated by a systemic acute-phase protein and by invariant natural killer T (iNKT) cells.
• Innate immunity: One-two blow alerts immune system | PDF (183 KB)
  - Nat Rev Immunol 10(11):752 (2010)
  The opportunistic fungal pathogen Candida albicans is a constituent of the normal flora in many people, but it can also cause mucosal disease. In healthy individuals, colonizing yeast forms of C. albicans
• Antigen-presenting cell function in the tolerogenic liver environment
  - Nat Rev Immunol 10(11):753 (2010)
  The demands that are imposed on the liver as a result of its function as a metabolic organ that extracts nutrients and clears gut-derived microbial products from the blood are met by a unique microanatomical and immunological environment. The inherent tolerogenicity of the liver and its role in the regulation of innate and adaptive immunity are mediated by parenchymal and non-parenchymal antigen-presenting cells (APCs), cell-autonomous molecular pathways and locally produced factors. Here, we review the central role of liver APCs in the regulation of hepatic immune function and also consider how recent insights may be applied in strategies to target liver tolerance for disease therapy.
• The tipping points in the initiation of B cell signalling: how small changes make big differences
  - Nat Rev Immunol 10(11):767 (2010)
  B cells are selected by the binding of antigen to clonally distributed B cell receptors (BCRs), triggering signalling cascades that result in B cell activation. With the recent application of high-resolution live-cell imaging, we are gaining an understanding of the events that initiate BCR signalling within seconds of its engagement with antigen. These observations are providing a molecular explanation for fundamental aspects of B cell responses, including antigen affinity discrimination and the value of class switching, as well as insights into the underlying causes of B cell tumorigenesis. Advances in our understanding of the earliest molecular events that follow antigen binding to the BCR may provide a general framework for the initiation of signalling in the adaptive immune system.
• The importance of natural IgM: scavenger, protector and regulator
  - Nat Rev Immunol 10(11):778 (2010)
  The existence of IgM has been known for more than a century, but its importance in immunity and autoimmunity continues to emerge. Studies of mice deficient in secreted IgM have provided unexpected insights into its role in several diverse processes, from B cell survival to atherosclerosis, as well as in autoimmunity and protection against infection. Among the various distinct properties that underlie the functions of IgM, two stand out: its polyreactivity and its ability to facilitate the removal of apoptotic cells. In addition, new B cell-targeted therapies for the treatment of autoimmunity have been shown to cause a reduction in serum IgM, potentially disrupting the functions of this immunoregulatory molecule and increasing susceptibility to infection.
• Vaccine delivery: a matter of size, geometry, kinetics and molecular patterns
  - Nat Rev Immunol 10(11):787 (2010)
  Researchers working on the development of vaccines face an inherent dilemma: to maximize immunogenicity without compromising safety and tolerability. Early vaccines often induced long-lived protective immune responses, but tolerability was a major problem. Newer vaccines have very few side effects but can be of limited immunogenicity. One way to tackle this problem is to design vaccines that have all the properties of pathogens with the exception of causing disease. Key features of pathogens that can be mimicked by vaccine delivery systems are their size, shape and surface molecule organization. In addition, pathogen-associated molecular patterns can be used to induce innate immune responses that promote adaptive immunity. In this Review, we discuss the approaches currently being used to optimize the delivery of antigens and enhance vaccine efficacy.
• The Immune Tolerance Network at 10 years: tolerance research at the bedside
  - Nat Rev Immunol 10(11):797 (2010)
  Immune tolerance-inducing therapies reprogramme immune cells to eliminate pathogenic immune responses while preserving protective immunity. The Immune Tolerance Network (ITN), sponsored by the US National Institutes of Health, was established in 1999 to evaluate new tolerance-inducing therapies and carry out mechanistic studies using a unique interactive approach in partnership with industry, academia and foundations. Ten years later, the ITN has carried out approximately 36 clinical trials and tolerance studies examining innovative tolerogenic approaches in the settings of allergy, autoimmune diseases and organ transplantation. ITN investigators have published more than 80 original research papers based on this work. This Timeline article summarizes the progress and challenges of clinical research in the ITN.